The Somatic Genomic Landscape of Glioblastoma

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• 作者：Cameron?W. Brennan ; Roel?G.W. Verhaak ; Aaron McKenna ; Benito Campos ; Houtan Noushmehr ; Sofie?R. Salama ; Siyuan Zheng ; Debyani Chakravarty ; J.?Zachary Sanborn ; Samuel?H. Berman ; Rameen Beroukhim ; Brady Bernard ; Chang-Jiun Wu ; Giannicola Genovese ; Ilya Shmulevich ; Jill Barnholtz-Sloan ; Lihua Zou ; Rahulsimham Vegesna ; Sachet?A. Shukla ; Giovanni Ciriello ; et al.
• 刊名：Cell
• 出版年：2013
• 出版时间：10 October, 2013
• 年：2013
• 卷：155
• 期：2
• 页码：462-477
• 全文大小：4145 K

文摘

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Summary

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.